AML-394 Tagraxofusp in Blastic Plasmacytoid Dendritic Cell Neoplasm With/Without Central Nervous System Involvement and Intrathecal Chemotherapy as Primary Treatment or Prophylaxis: An Italian Experience

Abstract

The precise frequency of central nervous system (CNS) involvement in blastic plasmacytoid dendritic cell neoplasm (BPDCN) is currently unknown. Recent data suggest it may be ~10% at baseline and 30% at first relapse. CNS is a 'sanctuary' for systemic treatment and can lead to disease recurrence even after the achievement of a complete response (CR) at the medullary and skin level. Ensuring complete meningeal disease clearance is essential, and combining intrathecal (IT) chemotherapy with systemic treatment is a promising approach. Tagraxofusp (TAG, SL-401) is a first-in-class therapy targeting CD123, a molecule that is overexpressed in BPDCN. TAG, available in the US and Europe, is the only approved drug for patients with BPDCN. To determine whether CNS prophylaxis/treatment impacts the prognosis and efficacy of systemic TAG treatment in patients with BPDCN. Retrospective single-center chart review. Patients with BPDCN, with (CNS+) or without (CNS-) CNS involvement. Patients received TAG intravenous infusions at 12 mcg/kg daily on days 1-5 of a 21-day cycle. Intrathecal (IT) chemotherapy (cytarabine and dexamethasone ± methotrexate) was administered in combination with TAG at each cycle as prophylaxis (CNS-) or primary-intention treatment (CNS+). Assessments included CNS response, tumor response, survival, and adverse event (AE) monitoring. Data were collected on 5 patients (n=3 CNS+, n=2 CNS-); all received TAG as first-line therapy. The median number of TAG cycles was 3 (range 1-4). All 3 patients with CNS+ disease achieved CNS complete response (CR), and none reported CNS relapse. In patients receiving CNS prophylaxis, 1 patient received TAG plus HSCT and is in CR after 29 months; another received high-dose chemotherapy, achieved a good partial remission after TAG, and remains alive after 4 months with HSCT shortly planned. No AEs associated with IT chemotherapy were reported. These preliminary results confirm the feasibility of IT chemotherapy in combination with systemic TAG therapy. Baseline CNS involvement did not appear to impact the efficacy or safety profile of TAG. IT chemotherapy and TAG effectively cleared and controlled CNS involvement. IT prophylaxis should be considered in patients with BPDCN who receive CD123-targeted therapies.